Christine Phillips, Josh Francis

Recommendations

Investigations for malaria should be performed on anyone who has travelled from/through an endemic malaria area within 3 months of arrival if asymptomatic, or within 12 months if symptoms of fever (regardless of any pre-departure malaria testing or treatment).

Test with both thick and thin blood films AND an antigen-based rapid diagnostic test (RDT), as RDT alone is not significantly sensitive to detect all non P.falciparum infections.

All people with malaria should be treated by, or in consultation with, a specialist ID service. Discuss diagnoses urgently with an infectious disease service. Patients with malaria may deteriorate quickly, especially children, pregnant women and those with low immunity.

Admit all patients with falciparum malaria to hospital, at least for the initial part of their treatment. Experienced clinicians may treat individuals with non-falciparum or non-severe falciparum malaria infection as outpatients if they are in a non-malaria receptive area.

+ Overview

Malaria is a mosquito-spread parasitic protozoal infection caused by the genus Plasmodium. Of the five species of human malarial parasites, Plasmodium falciparum is the most common and dangerous. One-third of malaria imported to Australia occurs in migrants coming through Papua New Guinea and India.64

Malaria is endemic in many refugee-source countries, and some transit countries (see table 2.1). All refugees to Australia from malaria-endemic regions are offered a voluntary Departure Health Check (DHC), which includes an RDT for malaria (and treatment if positive) in the 72 hours prior to departure.19 Previous issues with documentation of DHC treatment and sub-optimal anti-malarial therapy have been resolved.65 Treatment is now with WHO-recommended artemether/lumefantrine and should be documented on a health manifest that accompanies the individual. Diagnoses of malaria in people from refugee-like backgrounds have decreased since the introduction of pre-departure screening for malaria.66

A list of countries with significant malaria risk is provided in table 2.1. Detailed, up-to-date information on malaria by country is available from the Malaria Atlas Project.

Australia was declared free from endemic malaria in 1981. However, much of Australia north of latitude 19°S remains receptive to malaria, due to the presence of patent mosquito vectors (Anopheles spp.).67 This has been a constant threat to Australia’s ‘malaria-free’ status.68,69 Therefore, the detection and treatment of malaria in individuals arriving into Australia from malaria-endemic areas is of significant public health importance.

Malaria has been diagnosed in 4–10% of refugee cohorts from Sub-Saharan Africa in Australian studies,41,50,70 but is uncommon in audits of newly arrived Iraqi71 or Karen refugees.43,48 Malaria has also been diagnosed in people arriving by boat off the coast of Darwin.72 Thus, there is a rationale for re-screening people from refugee-like backgrounds from malaria-endemic areas on arrival, with enhanced vigilance for malaria in people with a febrile illness.73

+ History and examination

Malaria must be considered in any patient who has visited a malarious area and presents with a febrile illness, even months after arriving in Australia. Other symptoms of malaria include headache, nausea, chills, sweating, diarrhoea and malaise.

Severe malaria requires urgent referral to a hospital. Symptoms, signs and laboratory features of severe malaria include any degree of altered consciousness, jaundice, oliguria, severe anaemia or hypoglycaemia, parasite count >100,000/μL or >2%, or, if patient is vomiting or acidotic. Conversely, individuals with long-term acquired immunity and low-grade parasitaemia may be asymptomatic.70

+ Investigations

The ‘gold standard’ test for the diagnosis of malaria remains the thick and thin blood film examination for malaria parasites by light microscopy. A combination of blood films and RDT has relatively high sensitivity for the detection of P. falciparum infection. RDTs are frequently used in Australian laboratories to supplement blood film examination. The RDT for falciparum malaria may remain positive up to 28 days post treatment (see ‘Patients with pre-departure screening test’ below).

Mixed infections with more than one Plasmodium species are not infrequent74 and can usually be identified from the blood films. Malaria PCR is available in reference laboratories and should be considered to rule out sub-microscopic parasitaemia e.g. such as in patients who may have acquired immunity to malaria and/or in whom the efficacy of treatment given is uncertain. Some individuals can harbour sub-patent infections (i.e. blood film negative) with very low levels of detection for prolonged periods of time;75 these patients may become febrile as their immunity wanes and PCR-based testing (available in reference laboratories) may be required to exclude sub-patent infection.

If a patient has symptoms consistent with malaria but negative initial blood films and/or RDT result, repeat blood films should be performed in an attempt to demonstrate malarial parasites.74 Additional investigations in an unwell patient with malaria should be directed to detecting anaemia, acute kidney injury, abnormal liver function, hypoglycaemia or a metabolic acidosis.

+ Management and referral

Refer to table 2.2 for all management.

Plasmodium falciparum malaria

All patients with falciparum malaria should be referred urgently to a physician with experience in the management of malaria. Children with malaria should be discussed urgently with a paediatric ID physician. Children and people with low immunity who have malaria may deteriorate quickly.

Current Australian recommendations suggest that all patients with falciparum malaria should be admitted to hospital, at least for the initial part of their treatment,76 although it is possible to treat individuals with non-severe malaria infection entirely as outpatients.65,70,77 Patients with asymptomatic or uncomplicated falciparum malaria who are able to tolerate oral medication should be treated with oral artemisinin-based combination therapy (ACT).76,77 The only ACT product available in Australia at present is artemether-lumefantrine (Riamet®), which is available on authority prescription for suspected or proven falciparum infection. For further treatment guidelines refer to table 2.2. For severe malaria refer to hospital immediately and seek expert advice.

Plasmodium Vivax, Malariae or Ovale Malaria

Patients with confirmed vivax, malariae or ovale malaria (or where the parasite cannot be determined) should also have artemether-lumefantrine treatment, although this preparation is only available via the PBS for falciparum malaria and patients should be prescribed the medication via a hospital pharmacy.

Patients with severe non-falciparum malaria should be referred immediately to hospital for expert advice.

In patients with P. vivax or P. ovale infection; hypnozoite eradication therapy (or ‘radical cure’) should be attempted, to reduce the likelihood of subsequent relapses.76 Hypnozoite eradication involves a weight-based, generally two-week course of primaquine, available via application through the Special Access Scheme (SAS). Health workers should pay careful attention to adherence, and be aware of the risk of relapse. Before commencing primaquine, all patients should be screened for Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency, because of the risk of haemolysis for these patients. Primaquine is contra-indicated in patients with severe G6PD deficiency, but may be used with caution, and under supervision in those with mild deficiency.

Patients with Positive Pre-departure Screening Test

Refugees with a positive malaria result on pre-departure DHC screening are treated with a three-day course of ACT before departure, according to the protocol of the International Organization for Migration (IOM). This treatment is not monitored, and adherence should be checked with the patient (or their parents, in children). Thick and thin blood film testing after arrival is recommended. The RDT may stay positive for up to four weeks after successful treatment, so is of limited use in this situation. A negative blood film does not exclude sub-patent malaria.

A person who has tested positive at the pre-departure screen but in whom there is uncertainty regarding adherence to pre-departure treatment remains at risk of recurrent symptomatic illness, and should be retreated.

Follow-up

Patients should be assessed one month post treatment and have follow-up blood films performed to ensure that the infection has been successfully treated. Asymptomatic recrudescence and relapse can occur despite initial eradication of infection and full adherence. Artemisinin resistance has been reported in some areas of the Greater Mekong Subregion (Thailand, Vietnam, Cambodia, Laos and Myanmar (Burma))78 resulting in reduced efficacy of ACT against P. falciparum. Seek expert advice if ACT resistance is suspected.

For patients with malaria caused by P. falciparum who are being treated in malaria-receptive regions of northern Australia, a single dose of primaquine is recommended to reduce the risk of transmission to local mosquitoes (see table 2.2).

Be aware that delayed relapse for all strains of malaria can occur up to one year after leaving the endemic area. Have a low threshold for re-investigating for malaria in any person with fever.

+ Considerations in Pregnancy and Breastfeeding

Pregnant women with malaria are at increased risk for severe malaria, severe anaemia, and delivery of a low birth weight infant. Anti-malarials that are considered effective and can be used in all stages of pregnancy include atovaquone-proguanil (category B2), clindamycin (category A) and quinine sulphate (category D, but has been used safely for malaria in pregnancy).76 We recommend the combination of quinine and clindamycin for pregnant patients. Clindamycin is not subsidised on the PBS for malaria treatment. Treatment should, at least initially, be given as supervised inpatient therapy. Pregnant women with severe malaria may require treatment with intravenous artesunate (as for severe malaria in non-pregnant patients) guided by expert advice.

The above medications are contained in very low levels in breast milk, and are considered safe for infants. Breastfeeding women should receive standard doses of anti-malarial treatment recommended for all adults, with the exception of doxycycline (category D). Before taking primaquine (if required), both the infant and the mother should be tested for G6PD deficiency.

quinine sulfate 600mg (adult less than 50kg: 450mg) (child: 10mg/kg up to 600mg) orally, 8-hourly for 7 days

PLUS EITHER

doxycycline 100mg (child 8 years or older: 2mg/kg up to 100mg) orally, 12-hourly for 7 days (which can start after day 1 of quinine therapy) OR (for pregnant women or children younger than 8 years) clindamycin 300mg (child: 5mg/kg up to 300mg) orally, 8-hourly for 7 days.

For patients with malaria caused by P. falciparum (either alone or with other species) acquired from the Greater Mekong Subregion (Thailand, Vietnam, Cambodia, Laos and Myanmar (Burma)) and who respond slowly to artemether+lumefantrine (ie persisting parasitaemia after 72 hours of therapy), switch to oral quinine sulfate plus either doxycycline or clindamycin as above, for 7 days.

For patients with malaria caused by P. falciparum who are being treated in malaria-receptive regions of northern Australia, a single dose of primaquine is recommended to reduce the risk of transmission to local mosquitoes. Add: primaquine 15mg (child: 0.25mg/kg up to 15mg) orally, as a single dose.

Hypnozoite eradication therapy

First exclude G6PD deficiency in all

For P. vivax infection use concurrently: primaquine 30mg (child: 0.5mg/kg up to 30mg) orally, daily, or if nausea occurs 15mg (child: 0.25mg/kg up to 15mg) orally, 12-hourly. Treat for a minimum of 14 days or, in adults more than 70kg, until a total cumulative dose of 6mg/kg is reached

For P. ovale infection use concurrently: primaquine 15mg (child: 0.25mg/kg up to 15mg) orally, daily for 14 days If a relapse of malaria occurs despite treatment with primaquine, seek expert advice.

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The Australian Refugee Health Practice Guide was produced with funds from the Australian Government Department of Health.

Disclaimer

The information set out in the Australian Refugee Health Practice Guide (“the Guide”) is current at the date of first publication and is intended for use as a guide of a general nature only and may or may not be relevant to particular patients or circumstances. Nor is the Guide exhaustive of the subject matter. Persons implementing any recommendations contained in the Guide must exercise their own independent skill or judgement or seek appropriate professional advice relevant to their own particular circumstances when so doing. The statements or opinions that are expressed in the Guide reflect the views of the contributing authors and do not necessarily represent the views of the editors or Foundation House. Compliance with any recommendations cannot of itself guarantee discharge of the duty of care owed to patients and others coming into contact with the health professional and the premises from which the health professional operates.

Whilst the information is directed to health professionals possessing appropriate qualifications and skills in ascertaining and discharging their professional (including legal) duties, it is not to be regarded as clinical advice and, in particular, is no substitute for a full examination and consideration of medical history in reaching a diagnosis and treatment based on accepted clinical practices.

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